Zebrafish robustly establish a 50:50 ratio of arteries and veins that occupy the spaces between segments along the animal's trunk. Although intersegmental vessels (ISVs) are originally all arterial, it is thought that they can be remodelled into veins by secondary sprouts from the posterior cardinal vein. In their study, Holger Gerhardt and colleagues now investigate how this artery-vein specification process is regulated. They reveal that ISVs are more likely to adopt a fate different to the vessels surrounding them. Overexpression of Notch in single endothelial cells locally promotes arterial fate, whereas the global arterial-venous equilibrium is unperturbed. Instead, the authors show that fewer veins form globally when blood flow is reduced. Furthermore, they demonstrate that, contrary to previous belief, venous specification occurs in the absence of secondary sprout contact with ISVs. Their finding that Notch activity around and before the time of secondary sprout contact predicts future arterial identity leads them to suggest that Notch signalling may initially determine arterial specification in a flow-independent manner. Overall, these results indicate that vessel identity is determined in a Notch-dependent manner before secondary sprouts contact ISVs, and that flow maintains the global balance of arteries and veins.

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